This project is designed to 1) provide information on the mechanism of actions of drugs that are uricosuric or that cause urate retention; and 2) provide information relevant to classes of diuretics. The studies of drugs affecting urate excretion involves mainly clearance and stop-flow experiments in monkeys which attempt 1) to establish that uricosuric drugs can be reabsorbed by active transport, 2) to explain interaction of uricosuric drugs that can result in failure of therapeutic effects, and 3) to determine if two separate classes of compounds are uricosuric or if bioconversion of one to the other is necessary. The studies on diuretics to be performed in dogs are designed 1) to determine if the increased metabolic cost of sodium transport seen after drug administration is attributable to a direct tubular effect or to a vasodilator effect, and 2) to assess the role of "extracellular" carbonic anhydrase in reabsorption of bicarbonate. BIBLIOGRAPHIC REFERENCES: Relationship between clearances of Ca and Na: effect of distal diuretics and PTH. L.S. Costanzo and I.M. Weiner. Am. J. Physiol. 230: 67-73, 1976. Comparative pharmacology of uricosuric drugs. I.M. Weiner. Gen. Pharmacol. 7: 1-4, 1976.